Dynamic Changes of Immune Cell Populations in Panc02 Pancreatic Cancer Bearing Immunocompetent Mice_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIUQiao-fei ¹ ,  LIAOQuan ¹ , ZONGYi ¹ , NIUZhe-yu ¹ , WANGMeng-yi ¹ , LIYuan ² , LUZhao-hui ² ,  ZHAOYu-pei ¹

1. Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;
2. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;

Corresponding author：

LIAOQuan, Email: lqpumc@126.com; ZHAOYu-pei, Email: zhao8028@263.net

Keywords：

Immunocompetent mice; Pancreatic cancer; Immune cell populations; Integrated treatments; Prognosis

DOI：

10.7507/1007-9424.20140328

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the dynamic changes of immune cell populations in Panc02 pancreatic cancer bearing immunocompetent mice. Methods The C57BL6/J mice syngeneic pancreatic cancer cell line Panc02 were subcutaneously implanted to establish the immunocompetent murine pancreatic cancer bearing model.According to the tumor size, the tumor was classified into 4 stages, named T₁-T₄, respectively.The flow cytometry was performed to identify the dynamic changes of different cell populations, such as inflammatory cells (CD45⁺), T helper (Th) lymphocytes, cytotoxic T lymphocytes (CTL), B lymphocytes, granulocytes, macrophages, dendritic cells (DC), natural killer (NK) cells, and natural killer T (NKT) cells in the peripheral blood and tumor tissue. Results Three dynamic types of immune cells with the tumor progression were identified:consistent increase, consistent decrease, increase and then decrease.①In peripheral blood:The proportion of the Th lymphocytes, CTL, and B lymphocytes consistently decreased; The proportion of granulocytes consistently increased; The proportion of the DC, macrophages, NK cells, and NKT cells increased from T₁ to T₃ stage but sharply decreased at T₄ stage.②In tumor tissue:The intratumoral CD45⁺ cells consis-tently increased; The proportion of the granucolyte, macrophages, and DC consistently increased; The proportion of the Th lymphocytes and the CTL consistently decreased; The proportion of the B lymphocytes did not change significantly; The proportion of the NK cells or NKT cells increased from T₁ to T₃ stage but sharply decreased at T₄ stage. Conclusion With pancreatic cancer progression, the immune cell populations show different dynamic change models, which imply their important roles in predicting the prognosis and the integrated treatments of pancreatic cancer.

Citation： LIUQiao-fei, LIAOQuan, ZONGYi, NIUZhe-yu, WANGMeng-yi, LIYuan, LUZhao-hui, ZHAOYu-pei. Dynamic Changes of Immune Cell Populations in Panc02 Pancreatic Cancer Bearing Immunocompetent Mice. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(11): 1366-1371. doi: 10.7507/1007-9424.20140328 Copy

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1. Hidalgo M.Pancreatic cancer[J].N Engl J Med, 2010, 362(17):1605-1617.
2. Helm O, Held-Feindt J, Grage-Griebenow E, et al.Tumor-associated macrophages exhibit proand anti-inflammatory properties by which they impact on pancreatic tumorigenesis[J].Int J Cancer, 2014, 135(4):843-861.
3. Hamada S, Masamune A, Shimosegawa T.Inflammation and pancreatic cancer:disease promoter and new therapeutic target[J].J Gastroenterol, 2014, 49(4):605-617.
4. Steele CW, Jamieson NB, Evans TR, et al.Exploiting inflammation for therapeutic gain in pancreatic cancer[J].Br J Cancer, 2013, 108(5):997-1003.
5. Wang W, Hodkinson P, McLaren F, et al.Histologic assessment of tumor-associated CD45(+) cell numbers is an independent predictor of prognosis in small cell lung cancer[J].Chest, 2013, 143(1):146-151.
6. Mellman I, Coukos G, Dranoff G.Cancer immunotherapy comes of age[J].Nature, 2011, 480(7378):480-489.
7. Vanneman M, Dranoff G.Combining immunotherapy and targeted therapies in cancer treatment[J].Nat Rev Cancer, 2012, 12(4):237-251.
8. An X, Ding PR, Li YH, et al.Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer[J].Biomarkers, 2010, 15(6):516-522.
9. Stotz M, Gerger A, Eisner F, et al.Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer[J].Br J Cancer, 2013, 109(2):416-421.
10. Proctor MJ, McMillan DC, Morrison DS, et al.A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer[J].Br J Cancer, 2012, 107(4):695-699.
11. Absenger G, Szkandera J, Pichler M, et al.A derived neutrophil to lymphocyte ratio predicts clinical outcome in stageⅡandⅢcolon cancer patients[J].Br J Cancer, 2013, 109(2):395-400.
12. 金鑫, 冯利, 李福广, 等.血清中性粒细胞/淋巴细胞比值与胃肠间质瘤患者预后的关系及其临床意义[J].中国普外基础与临床杂志, 2013, 17(8):910-914.
13. Pavoni E, Monteriù G, Santapaola D, et al.Tumor-infiltrating B lymphocytes as an efficient source of highly specific immunoglobulins recognizing tumor cells[J].BMC Biotechnol, 2007, 7:70.
14. Shi JY, Gao Q, Wang ZC, et al.Margin-infiltrating CD20(+) B cells display an atypical memory phenotype and correlate with favorable prognosis in hepatocellular carcinoma[J].Clin Cancer Res, 2013, 19(21):5994-6005.
15. Xu T, Huang Z, Su B, et al.Prognostic significance of circulating CD19+B lymphocytes in EBV-associated nasopharyngeal carcinoma[J].Med Oncol, 2014, 31(10):198.
16. Koido S, Homma S, Okamoto M, et al.Treatment with chemotherapy and dendritic cells pulsed with multiple Wilms' tumor 1(WT1)-specific MHC classⅠ/Ⅱ-restricted epitopes for pancreatic cancer[J].Clin Cancer Res, 2014, 20(16):4228-4239.
17. Shindo Y, Hazama S, Maeda Y, et al.Adoptive immunotherapy with MUC1-mRNA transfected dendritic cells and cytotoxic lymphocytes plus gemcitabine for unresectable pancreatic cancer[J].J Transl Med, 2014, 12:175.
18. Zhang Z, Liu Q, Che Y, et al.Antigen presentation by dendritic cells in tumors is disrupted by altered metabolism that involves pyruvate kinase M2 and its interaction with SOCS3[J].Cancer Res, 2010, 70(1):89-98.
19. Nowarski R, Gagliani N, Huber S, et al.Innate immune cells in inflammation and cancer[J].Cancer Immunol Res, 2013, 1(2):77-84.
20. Deschênes-Simard X, Mizukami Y, Bardeesy N.Macrophages in pancreatic cancer:starting things off on the wrong track[J].J Cell Biol, 2013, 202(3):403-405.
21. 赵骏杰, 秦净, 束平.肿瘤相关巨噬细胞是胃癌重要的促进因素[J].中国普外基础与临床杂志, 2013, 17(11):1315-1319.
22. Yamamoto T, Yanagimoto H, Satoi S, et al.Circulating CD4⁺ CD25⁺ regulatory T cells in patients with pancreatic cancer[J].Pancreas, 2012, 41(3):409-415.
23. Vivier E, Ugolini S, Blaise D, et al.Targeting natural killer cells and natural killer T cells in cancer[J].Nat Rev Immunol, 2012, 12(4):239-252.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Dynamic Changes of Immune Cell Populations in Panc02 Pancreatic Cancer Bearing Immunocompetent Mice

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